Revisiting the immune landscape post spinal cord injury: More than black and white.

Spinal cord injury (SCI) induced catastrophic neurological disability is currently incurable, especially in elderly patients. Due to the limited axon regeneration capacity and hostile microenvironment in the lesion site, essential neural network reconstruction remains challenging. Owing to the blood-spinal cord barrier (BSCB) created immune cells and cytokines isolation, the immune elements were incorrectly recognized as innocent bystanders during the SCI pathological process traditionally. Emerging evidence demonstrated that the central nervous system (CNS) is an "immunological quiescent" rather than "immune privileged" area, and the CNS-associated immune response played mixed roles which dedicate beneficial and detrimental contributions throughout the SCI process. Consequently, coordinating double-edged immunomodulation is vital to promote tissue repair and neurological recovery post-SCI. The comprehensive exploration and understanding of the immune landscape post-SCI are essential in establishing new avenues for further basic and clinical studies. In this context, this review summarizes the recent significant breakthroughs in key aspects of SCI-related immunomodulation, including innate and adaptive immune response, immune organ changes, and holistic immune status modification. Moreover, the currently existing immune-oriented therapies for SCI will be outlined.

Unlocking the Recovery Potential: JMJD3 Inhibition-Mediated SAPK/JNK Signaling Inactivation Supports Endogenous Oligodendrocyte-Lineage Commitment Post Mammalian Spinal Cord Injury.

Spinal cord injury (SCI) induced catastrophic neurological disability is often incurable at present. The injury triggered immediately oligodendrocytes loss and overwhelming demyelination are regarded as an insurmountable barrier to SCI recovery. To date, effective strategy to promote the endogenous oligodendrocytes replacement post SCI remains elusive. Epigenetic modifications are emerging as critical molecular switches of gene expression in CNS. However, the epigenetic mechanisms underlying oligodendrogenesis post SCI yet to be discovered. In this study, we report that H3K27me3 demethylase JMJD3 exists as a pivotal epigenetic regulator which manipulates the endogenous oligodendrogenesis post SCI. We found that JMJD3 inhibition promotes the oligodendrocyte linage commitment of neural stem/progenitor cells (NPCs) in vitro and in vivo. Moreover, we demonstrated that JMJD3 inhibition mediated SAPK/JNK signaling inactivation is functionally necessary for endogenous oligodendrocyte-lineage commitment post SCI. Our results also suggested that JMJD3 is downstream of SAPK/JNK pathway, and capable of translates SCI induced SAPK/JNK signaling into epigenetic codes readable by spinal cord endogenous NPCs. Taken together, our findings provide novel evidence of JMJD3 mediated oligodendrocyte-lineage commitment orchestration post SCI, which would be a potential epigenetic approach to induce the mature mammalian endogenous recovery.

Gut bacteria affect the tumoral immune milieu: distorting the efficacy of immunotherapy or not？.

Immunotherapy using immune-checkpoint inhibitors is revolutionizing oncotherapy. However, the application of immunotherapy may be restricted because of the lack of proper biomarkers in a portion of cancer patients. Recently, emerging evidence has revealed that gut commensal bacteria can impact the therapeutic efficacy of immune-checkpoint inhibitors in several cancer models. In addition, testing the composition of gut bacteria provides context for prediction of the efficacy and toxicity of immunotherapy. In this review, we discuss the impacts of gut commensal bacteria on the tumoral immune milieu, highlighting some typical bacteria and their associations with immunotherapy.

Adipose-derived mesenchymal stem cell therapy for radiation-induced vascular injury in small intestine of rat / 中华放射医学与防护杂志

Objective To assess the therapeutic effect of human adipose-derived mesenchymal stem cells on radiation-induced vascular injury in the small intestine of rat. Methods A total of 34 male Sprague-Dawley rats were enrolled in this study. To establish a model of radiation-induced intestinal injury, each rat was irradiated with 15 Gy in whole abdomen. 17 rats were randomly selected and infused intraperitoneally with passage 6 ( P6 ) Ad-MSCs, and the other 17 rats that received PBS were set as control. 10 days post-irradiation, the number of CD31+ endothelial cells in the small intestine villus was measured by flow-cytometry, the expressions of CD31, CD105 and isolectin-B4 in the na?ve endothelial cells with detected by IHC-staining, and the vascular integrity was evaluated by measuring VE-Cadherin. The origination of na?ve endothelial cells within injured intestine was also analyzed. In addition, total mRNA were extracted from irradiated small intestine to assay the expressions of VEGF, bFGF, Flk-1 and SDF-1 using quantitative Real-time PCR. Results Compared to the control, the amount of CD31-postive endothelial cells within irradiated intestine was significantly increased after Ad-MSCs infusion ( t=12?15, P<0?05). The microvascular density in the injured sites was also significantly increased by the infusion of Ad-MSCs (20 d:t=10?33, P<0. 05;30 d:t=32?85, P<0?05). Moreover, the expressions of VEGF, bFGF, Flk-1 and SDF-1 were significantly up-regulated after delivery of Ad-MSCs ( VEGF:t =10?34, bFGF:t=11?25,Flk-1:t=6?73, SDF-1:t=6?73, all P<0?05), which was beneficial in maintaining the integrity of intra-villus blood-vessels as well as promoting neovascularization in the injured sites. Conclusion Ad-MSCs had potentials in healing radiation-induced vascular injury in rat small intestine.

Therapeutic effect of adipose-derived mesenchymal stem cells on radiation enteritis / 中华放射医学与防护杂志

Objective To evaluate the therapeutic effect of adipose-derived mesenchymal stem cells on radiation enteritis.Methods A total of 52 male Sprague-Dawley rats were used in the present study.Herein,46 rats were randomly selected and irradiated with a dose of 15 Gy at their abdomens.Two hours post-irradiation,23 rats were randomly selected and infused intraperitoneally with adipose-derived mesenchymal stem cells in passage 6 from young-female donor.The other 23 rats were intraperitoneally infused with PBS.The rest 6 rats were set as normal control.During the first 10 days post-irradiation,peripheral blood-samples from irradiated rats were harvested for testing the levels of IL-10 in serum using ELISA assay.Additionally,after isolating the thymic cells and peripheral blood mononuclear cells,the percentages of CD4/CD25/Foxp(3)-positive regulatory T cells in thymus and peripheral blood were tested by flow-cytometry.Finally,infiltration of inflammatory cells and deposition of collagens within irradiated small intestine were analyzed by H&E staining and Masson Trichrome staining,respectively.Based on the MPO-immunohistochemistry staining,the type of infiltrated cells was identified.The Kaplan-Meier method was used for analyzing the survival rate of irradiated rats.Results During a period of 30 days post-irradiation,the irradiated rats receiving adipose-derived mesenchymal stem cells survived longer than those receiving PBS (t =4.53,P ＜ 0.05).Compared to the irradiated rats with PBS-treatment,adipose-derived mesenchymal stem cells could elevate the level of IL-10 in serum (7 d:t =13.93,P ＜ 0.05) and increase the percentages of CD4/CD25/Foxp(3)-positive regulatory T cells in both peripheral blood (3.5 d:t =7.72,7 d:t=11.11,10 d:t =6.99,P ＜0.05) and thymus (7 d:t =16.17,10 d:t =12.12,P＜ 0.05).Moreover,infiltration of inflammatory cells and deposition of collagens within irradiated small intestine were mitigated by adipose-derived mesenchymal stem cells.Conclusions Adipose-derived mesenchymal stem cells were capable of curing radiation enteritis.

Therapeutic effects of gensenoside-Rg3 combined with radiotherapy on advanced non-small cell lung cancer / 中华放射医学与防护杂志

Objective To study the efficacy and toxicity of gensenoside-Rg3 (Rg3) combined with radiotherapy on non-small cell lung cancer ( NSCLC ) at advanced stages (Ⅲ and Ⅴ ).Methods Sixty-three patients with stage Ⅲ or Ⅳ NSCLC were divided randomly into two groups:treatment group ( n =35 ) treated with Rg3 combined with radiotherapy and control group ( n =28 ) treated with radiotherapy alone.The efficacy and side effects were compared after the treatment.Results The response rate ( CR + PR) of the treatment group was 57.14％,significantly higher than that of the control group (32.14％,x2 =3.91,P ＜ 0.05).The median survival time of the treatment group was 14.2 months,significantly longer than that of the control group ( 11.2 months,x2 =2.07,P ＜ 0.05 ).The one-year survival rate of the treatment group was 62.86％,significantly higher than that of the control group (39.29％,x2 =4.40,P ＜0.05).The incidence rates of side effects of the treatment group were all lower than those of the control group,but there were not significant difference. Conclusions Gensenoside-Rg3 combined with radiotherapy is effective for advanced stage NSCLC,with attenuation and synergistic effects.